PMID- 11029041
OWN - NLM
STAT- MEDLINE
DCOM- 20001207
LR  - 20181113
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 11
IP  - 10
DP  - 2000 Oct
TI  - Matricellular proteins as modulators of cell-matrix interactions: adhesive defect 
      in thrombospondin 2-null fibroblasts is a consequence of increased levels of 
      matrix metalloproteinase-2.
PG  - 3353-64
AB  - Thrombospondin 2 (TSP2)-null mice, generated by disruption of the Thbs2 gene, 
      display a variety of connective tissue abnormalities, including fragile skin and 
      the presence of abnormally large collagen fibrils with irregular contours in skin 
      and tendon. In this study we demonstrate that TSP2-null skin fibroblasts show a 
      defect in attachment to a number of matrix proteins, and a reduction in cell 
      spreading. To investigate the molecular mechanisms responsible for these abnormal 
      cell-matrix interactions, we compared the levels of matrix metalloproteinases 
      (MMPs) in wild-type and mutant fibroblasts. Isolation and analysis of gelatinases 
      from conditioned media by gelatin-agarose affinity chromatography and 
      gelatinolytic assays demonstrated that TSP2-null fibroblasts produce a 2-fold 
      increase in gelatinase A (MMP2) compared with wild-type cells. The adhesive 
      defect was corrected by treatment of TSP2-null fibroblasts with soluble TSP2, 
      with the MMP inhibitors BB94 and tissue inhibitor of metalloproteinase-2, and 
      with a neutralizing antibody to MMP2. Moreover, stable transfection of TSP2-null 
      fibroblasts with mouse TSP2 cDNA corrected both the adhesive defect and the 
      altered expression of MMP2. Finally, MMP2 was shown to interact with TSP2 in a 
      direct-binding plate assay. We conclude that TSP2 plays an important role in 
      cell-matrix interactions, and that a deficiency in the protein results in 
      increased levels of MMP2 that contribute to the adhesive defect in TSP2-null 
      fibroblasts and could play a role in the complex phenotype of TSP2-null mice.
FAU - Yang, Z
AU  - Yang Z
AD  - Department of Biochemistry, University of Washington, Seattle, Washington 98195, 
      USA.
FAU - Kyriakides, T R
AU  - Kyriakides TR
FAU - Bornstein, P
AU  - Bornstein P
LA  - eng
GR  - P01 HL018645/HL/NHLBI NIH HHS/United States
GR  - R01 AR045418/AR/NIAMS NIH HHS/United States
GR  - AR-45418/AR/NIAMS NIH HHS/United States
GR  - HL-18645/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Antibodies)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Thrombospondins)
RN  - 0 (thrombospondin 2)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Cell Adhesion/genetics/*physiology
MH  - Cell Adhesion Molecules/*physiology
MH  - Cells, Cultured
MH  - Culture Media, Conditioned
MH  - Extracellular Matrix/*physiology
MH  - Extracellular Matrix Proteins/*metabolism
MH  - Fibroblasts/*physiology
MH  - Kinetics
MH  - Matrix Metalloproteinase 2/*genetics/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Recombinant Proteins/metabolism
MH  - Skin/*cytology
MH  - Skin Physiological Phenomena
MH  - Thrombospondins/deficiency/genetics/*physiology
MH  - Transfection
PMC - PMC14997
EDAT- 2000/10/12 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/12 11:00
PHST- 2000/10/12 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/12 11:00 [entrez]
AID - 1321 [pii]
AID - 10.1091/mbc.11.10.3353 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2000 Oct;11(10):3353-64. doi: 10.1091/mbc.11.10.3353.